CD133^+/ABCG2^+的人肺癌多耐药性肿瘤细胞亚群的分离及鉴定  

Establishment and Characterization of CD133^+/ABCG2^+ Multi-drug Resistant Lung Carcinoma Cells Subpopulation

作　　者：赵雅瑞 张立凡[2] 刘特 

机构地区：[1]上海医药职工大学,上海200050 [2]复旦大学附属华东医院,上海200040 [3]上海中医老年医学研究所,上海200031

出　　处：《中国细胞生物学学报》2013年第10期1444-1452,共9页Chinese Journal of Cell Biology

基　　金：上海市科委医学引导基金(批准号:10411967100)资助的课题~~

摘　　要：肿瘤干细胞的多耐药性是导致肿瘤化疗失败的重要因素之一。因此,鉴定和明确耐药性肺癌干细胞亚群(cancer stem-cell subpopulations)的特征和机制是当前的热点。该研究从肺癌病人的肿瘤组织中分离出一个高表达CD133和ABCG2蛋白的细胞亚群。发现该CD133+/ABCG2+肺癌细胞高表达干细胞的生物标志,如:Nanog、Oct4、Sox2、Nestin、CD44、CD117、CD133和ABCG2等。不仅如此,这群细胞在体外具有高增殖性和高侵袭性,对于多种常用的化疗药物(如:顺铂和吉西他滨等)都具有耐受性。而且,少量的CD133+/ABCG2+肺癌细胞即可以在免疫缺陷小鼠体内形成肿瘤。为了研究耐药性机制,我们检测了CD133+/ABCG2+中ABCG2基因启动子区域的CpG岛(CpG islands)DNA甲基化修饰状态。实验结果表明,该细胞中,ABCG2基因启动子区域的CpG岛处于去甲基化修饰状态。综上所述,作者成功地从肺癌病人肿瘤组织中分离、富集得到了CD133+/ABCG2+细胞亚群,并利用该群细胞在体外建立了肿瘤耐药性研究模型。对于肺癌CD133+/ABCG2+细胞的研究可为开发肺癌个体化治疗和新型化疗药物的设计和研发提供理论依据。Multi-drug resistance is an important element which leads to ineffectiveness of chemotherapeu- tics. Identification of subpopulations of cancerous lung cells with multi-drug resistance and cancer stem cell proper- ties has recently become a major research interest. We identified a subpopulation from the primary lung tumor tis- sues, which had high surface expression of both CD133 and ABCG2. We found this subpopulation of cells termed CD 133＋/ABCG2＋ also overexpressed stem cells markers such as Nanog, Oct4, Sox2, Nestin, CD44, CD 117, CD 133 and ABCG2. These cells are not only highly prolific and invasive, but also resistant to treatment with a variety of chemotherapeutics such as casplatin and gemcitabine. Additionally, CD 133＋/ABCG2＋ cells can readily form tumorsin vivo in a relatively short time. To investigate the mechanism of aggressive tumor growth and drug resistance, we examined the CpG islands on the ABCG2 promoter of CD133＋/ABCG2＋ cells and found they were remark- ably hypomethylated. Thus, these data suggest that CD133＋/ABCG2＋ cells could be reliably sorted from the human lung cancer primary tissues, and represent a valuable model for studying cancer cell physiology and multi-drug resistance. Furthermore, identification and study of these cells could have a profound impact on selection of indi- vidual treatment strategies, clinical outcome, and the design or selection of the next generation of chemotherapeutic agents.

关 键 词：肺癌 肿瘤干细胞 耐药性 DNA甲基化 

分 类 号：R734.2[医药卫生—肿瘤]